One degree of freedom for dominance in indirect association studies

Usual tests of association using tag single nucleotide polymorphisms (SNPs) assume that the alleles of the causal locus act additively and that these alleles are then predicted indirectly via a set of tag SNPs. In the presence of strong dominance effects this model is not correct and an extra term needs to be included, which uses the tag SNPs to predict the heterozygosity of the causal locus. Assuming this scenario of a strong dominance effect, we present an appropriate test statistic and investigate how much power, if any, we gain by adding this single degree of freedom for dominance.     

Emerging trends in health and productivity management

Many large U.S. employers have generally embraced a Health and Productivity Management (HPM) perspective to guide their multiple employee health management efforts. In looking ahead there are a number of emerging trends that are helping to shape these efforts. As health promotion professionals assess the implications of these trends on their respective role and function within the worksite, it may provide a very useful process for refining strategies for programming and professional development. The identified trends also have a variety of implications for health promotion vendors and the growth of the health management marketplace.     

'A matter of faith, not science': analysis of media coverage of prostate cancer screening in Australian news media 2003-2006

OBJECTIVE: Despite a near universal absence of evidence-based policies supporting population screening for prostate cancer, the prostate-specific antigen (PSA) test is aggressively promoted in the media as a life-saving form of screening. The objective of this study was to examine media coverage of prostate-cancer screening in Australia. DESIGN: Frame analysis of all direct or attributed quotes about prostate cancer. SETTING: Australian capital city newspapers (February 2003-December 2006) and Sydney television news (January 2003-December 2006). MAIN OUTCOME MEASURES: Quotes regarding prostate cancer screening: n=436 in newspapers and television news. RESULTS: Seven rhetorical frames were identified. 86% of all quotes framed prostate screening and its outcomes as desirable, associating PSA testing as being consonant with other early-detection cancer-control messages. Adverse surgical sequelae to screening were often minimized, scientific progress highlighted and gender equity appeals appropriated. Those questioning screening were vilified, with epidemiology being framed as an inferior form of knowledge than clinical experience. CONCLUSIONS: Australian men are exposed to unbalanced and often non-evidence-based appeals to seek PSA testing. There is a disturbing lack of effort to redress this imbalance.     

The default effect in end-of-life medical treatment preferences.

BACKGROUND: Living wills are intended to preserve patient autonomy, but recent studies suggest that they do not always have their desired effect. One possible explanation is that living wills do not capture the authentic preferences of the patients who write them but instead reflect transient contextual effects on preferences. PURPOSE: Two experiments examined whether end-of-life treatment preferences expressed in a living will were influenced by the presence of default options. METHOD: College students participated in 2 Web-based questionnaire experiments (Ns = 182 and 51). Participants were randomly assigned to 1 of 2 or 3 default conditions. RESULTS: In experiment 1, participants expressed significantly different treatment preferences in 3 normatively equivalent, check box-formatted living wills that were either positively worded ("indicate medical treatments you would want administered"), negatively worded ("indicate treatments you would want withheld"), or of forced-choice format (P = 0.01). Participants expressed a stronger preference to receive treatment in the negatively worded document than in the positively worded document as a consequence of preferring the default option in both cases. Participants in experiment 2 were also influenced by the presence of a default option, but this time, while writing narrative living wills after viewing 1 of 2 sample living wills. In this experiment, the sample living will represented the default preference. The participants' own living wills tended to express preferences similar to those in the sample (P = 0.0005). CONCLUSION: The default manipulations in both experiments had potent but transient effects and influenced what participants wrote in their living wills but not their responses to later medical scenarios. Expression of end-of-life treatment preferences appears to be temporarily constructed from the decision-making context. These results have implications for surrogate decision making and the use of the living will as a tool to preserve patient autonomy.     

Searching: expectant fathers' experiences during labor and birth

When expectant fathers are present and view labor and birth as a couple experience, they are co-laboring in one of three roles: coach, teammate, or witness. Within these roles are various degrees and types of engagement. Men in the role of coach experience high degrees of physical and mental engagement. Teammates fluctuate between high and low degrees of physical and mental engagement, and witnesses remain at low degrees of engagement until the second stage of labor, when they experience high degrees of mental engagement. The expectant fathers' experience is influenced by the labor guides' activities of gatekeeping, leading, and informing. Men either maintain or redefine their role during labor and birth. Men who experience a sense of not belonging or who are uncomfortable with their role will redefine their role by using the strategy of searching for place. Searching for place involves the steps of identifying an alternative role, engaging in the new role, testing the role, and evaluating the effectiveness of the alternative role. Men who experience a sense of belonging in their new role will maintain this role. May posed the question, "Is it time to fire the coach?" This theory, which requires further testing and validation, does address May's question. Perhaps it is not time to fire the coach, as May indicated, but it is time to provide couples with options in the role expectant fathers play during labor and birth. This theory can guide nurses in relatively risk-free interventions for the expectant father. Nurses can assist expectant fathers in finding a place in labor and birth that will enhance a mutually satisfying birthing experience.     

Perceptions of the researcher: in-depth interviewing in the home

In this paper we explore the home as a setting to collect qualitative data. The text is drawn from a collaborative research initiative that sought to interview people with cardiac disease. The literature pays little attention to the home as a venue for in-depth data gathering and yet from our experience it is very different to other settings. We argue the need for extra consideration to aspects such as trust, self-disclosure and safety, and draw these conclusion from the data gathered in the field.     

Pulmonary granulocyte kinetics in relation to endothelial and granulocyte activation

The aim of the study was to measure the peripheral blood levels of soluble E-selectin in patients with systemic inflammation and compare them with in vivo granulocyte activation, pulmonary intravascular granulocyte pooling, pulmonary extravascular granulocyte migration and 99mTc-diethylenetriaminepenta-acetic acid (DTPA) aerosol clearance, an index of lung injury. The level of soluble E-selectin was measured by capture ELISA. Granulocytes were labelled with 111In and 99mTc for quantification of pulmonary granulocyte kinetics. The pulmonary vascular granulocyte pool (PGP) was expressed as a fraction of the total blood granulocyte pool. Pulmonary granulocyte migration was quantified on 24-h images using the 111In signal. Granulocyte activation was quantified as the percentage of circulating cells showing shape change ('primed'). Lung injury was assessed from the clearance rate of inhaled 99mTc-DTPA aerosol. Eighteen patients with systemic inflammation were studied: five with inflammatory bowel disease, eight with systemic vasculitis, four with graft versus host disease and one with a recent renal transplant. The peripheral blood levels of soluble E-selectin were significantly elevated in patients with systemic inflammation. The level of soluble E-selectin showed a significant association with granulocyte migration (Spearman rank correlation coefficient, Rs=0.53; P<0.05) but not with PGP or with the percentage of cells showing shape change (P>0.05 for both). Granulocyte migration was bimodal: patients were therefore subdivided into 'migrators' and 'non-migrators'. Soluble E-selectin level, 99mTc-DTPA clearance and PGP, but not the percentage of cells showing shape change, were significantly higher in migrators than in non-migrators. We conclude that pulmonary intravascular granulocyte pooling is increased in the presence of increased numbers of circulating primed granulocytes but increased pooling does not by itself promote granulocyte migration into the lung interstitium. Insofar as an elevated level of E-selectin in peripheral blood reflects vascular endothelial activation, the data are consistent with the notion that pulmonary endothelial activation is required, in addition to granulocyte activation and an expanded PGP, for granulocyte migration into lung parenchyma and, therefore, for lung injury to occur.     

RSV604, a novel inhibitor of respiratory syncytial virus replication

Respiratory syncytial virus (RSV) is the most common cause of lower respiratory tract infections worldwide, yet no effective vaccine or antiviral treatment is available. Here we report the discovery and initial development of RSV604, a novel benzodiazepine with submicromolar anti-RSV activity. It proved to be equipotent against all clinical isolates tested of both the A and B subtypes of the virus. The compound has a low rate of in vitro resistance development. Sequencing revealed that the resistant virus had mutations within the nucleocapsid protein. This is a novel mechanism of action for anti-RSV compounds. In a three-dimensional human airway epithelial cell model, RSV604 was able to pass from the basolateral side of the epithelium effectively to inhibit virus replication after mucosal inoculation. RSV604, which is currently in phase II clinical trials, represents the first in a new class of RSV inhibitors and may have significant potential for the effective treatment of RSV disease.     

Simian foamy virus infection in a blood donor

BACKGROUND: Infections with simian foamy virus (SFV) are widely prevalent in nonhuman primates. SFV infection was confirmed in a worker, occupationally exposed to nonhuman primates, who donated blood after the retrospectively documented date of infection. Human-to-human transmission of SFV through transfusion and its pathogenicity have not been studied. STUDY DESIGN AND METHODS: Recipients of blood from this donor were identified and blood samples from such recipients were tested for SFV infection by Western blot and PCR assay. RESULTS: One recipient of RBCs and another recipient of FFP had died; retroviral infections were not implicated. One platelet recipient could not be tested. Recipients of RBCs (two), a WBC-reduced RBC unit (one), and a platelet unit (one) tested SFV-negative 19 months to 7 years after transfusion. Tested recipients had transfusions 3 to 35 days after blood donation. Samples of one lot of albumin and three lots of plasma protein fraction (manufactured from recovered plasma from two donations) tested negative both for antibodies and for viral RNA. CONCLUSION: SFV transmission through transfusion was not identified among four recipients of cellular blood components from one SFV-infected donor. Derivatives containing plasma from that donor tested negative for SFV.